Intraoperative Analgesia with Magnesium Sulfate versus Remifentanil Guided by Plethysmographic Stress Index in Post-Bariatric Dermolipectomy: A Randomized Study.

Background: Magnesium sulfate reduces pain scores and analgesic consumption. Its use as an analgesic resource in opioid-free or opioid-sparing techniques have also been tested. The evaluation of the antinociceptive potency of drugs and doses indirectly, through hemodynamic oscillations has been questioned. A relatively new algorithm called the plethysmographic stress index has been considered sensitive and relatively specific as a parameter for assessing the need for intraoperative analgesia. Objectives: The aim of this trial was to assess the intraoperative analgesic capacity of magnesium sulfate compared to remifentanil. The secondary objectives were propofol consumption and its latency, the consumption of opioids, ephedrine, and cisatracurium. Patients and Methods. Forty patients scheduled for post-bariatric dermolipectomy were randomly assigned to two groups to receive total intravenous anesthesia with target-controlled hypnosis induced with propofol. Analgesia was obtained in the remifentanil group with remifentanil at an initial dose of 0.2 µg·kg-1·min-1 and in the magnesium sulfate group with magnesium sulfate 40 mg·kg-1 + 10 mg·kg-1·h-1. Results: There was no statistical hemodynamic difference between the groups before and after orotracheal intubation (p = 0.062) and before and after the surgical incision (p = 0.656). There was also no statistical difference in the variation of mean arterial pressure before and after intubation (p = 0.656) and before and after the surgical incision (p = 0.911). There was similar consumption of cisatracurium, ephedrine, and postoperative opioids between the groups. Some patients in the magnesium sulfate group needed more intraoperative fentanyl and propofol, although the latency of propofol was similar in both the groups. Conclusion: We conclude that using magnesium sulfate in intravenous general anesthesia for post-bariatric dermolipectomy is related to a significant reduction in opioid consumption without compromising hemodynamic stability. Overall, PSI monitoring was helpful in driving the analgesic strategy. The use of magnesium sulfate proved to be an important adjunct in the scenario presented, allowing the use of opioids to be avoided in certain cases. We found no statistical differences in the consumption of neuromuscular blocker and vasoconstrictor. Substituting opioids for magnesium sulfate leads to an increase in propofol consumption in the scenario presented. Studies with a larger sample are needed to corroborate the results presented and evaluate other potential advantages in reducing opioid consumption.

Atelectasis observed by computerized tomography after Caesarean section.

BACKGROUND: Atelectasis after either vaginal or Caesarean delivery has not been adequately quantified. This study addresses the hypothesis that atelectasis may be worse in women who undergo Caesarean section when compared with vaginal delivery under regional anaesthesia. METHODS: Twenty healthy non-smoking women submitted to a chest computed tomography (CT) 2 h after delivery in a University Hospital, who had experienced vaginal delivery (n=10) under combined spinal-epidural analgesia or a Caesarean section (n=10) under spinal anaesthesia, were evaluated. The percentage cross-sectional area of atelectasis in dependent lung regions were measured from the CT images obtained at cross-section of the xiphoid process and the top of the diaphragm. RESULTS: The percentage cross-sectional area of atelectasis was 3.95% in the vaginal delivery group and 14.1% in the Caesarean group (P<0.001, Mann-Whitney rank sum test). CONCLUSIONS: These results suggested that pulmonary atelectasis is greater after Caesarean section delivery under spinal anaesthesia than after vaginal delivery with combined spinal-epidural analgesia.

Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients.

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 m. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean +/- SEM, 42.9 +/- 6.9 vs 43.3 +/- 6.6 ppb) and non-asthmatic (13.3 +/- 1.3 vs 13.7 +/- 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients

Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 æm. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean ± SEM, 42.9 ± 6.9 vs 43.3 ± 6.6 ppb) and non-asthmatic (13.3 ± 1.3 vs 13.7 ± 1.1 ppb) subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001). There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation

Effects of ventilation, humidity and temperature on airway responsiveness to methacholine in rats.

Exercise-induced bronchoconstriction is associated with heat and water loss from the airways. It is not known whether these conditions can influence the response to bronchoactive agonists. The effects of different degrees of alveolar ventilation on the pulmonary response to methacholine and the role of humidity and temperature in this response were evaluated. Wistar rats were anaesthetized, tracheostomized and mechanically ventilated. Increasing doses of methacholine were infused intravenously and respiratory system resistance (Rrs) and elastance (Ers) were measured. The rats were ventilated with dry air at 13 degrees C, dry air at 37 degrees C, humid air at 13 degrees C and humid air at 37 degrees C. These four groups were further divided into three subgroups with a respiratory frequency adjusted to reach a carbon dioxide tension in arterial blood of 30, 40 and 50 mmHg. Temperature, humidity and level of alveolar ventilation did not influence the position of the dose/response curve to methacholine. However, the maximal changes in Ers were significantly lower in the rats ventilated with humid air. In addition, maximal changes in Ers were significantly higher in the rats with lower alveolar ventilation. These differences were not observed for maximal values of Rrs. The pulmonary response to methacholine in normal rats is significantly affected by the humidity of inspired air and the level of alveolar ventilation. This influence is more intense in the small airways and/or distal airspaces. This suggests that exercise or hyperventilation can change the behaviour of airway smooth muscle.

The patient-physician interactions as seen by undergraduate medical students.

CONTEXT: The interaction between a physician and his or her patient is complex and occurs by means of technical performance and through a personal relationship. OBJECTIVE: To assess the interaction between the medical professional and his or her patient with the participation of medical students assuming a role as observers and participants in a medical appointment in an outpatient office. DESIGN: Questionnaire interview study. SETTING: General Medicine outpatient offices, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. PARTICIPANTS: Medical students performed an ethnographical technique of observation, following 199 outpatient medical appointments with Clinical Medicine Residents. MAIN MEASUREMENTS: A questionnaire filled out by observer students measured the physician's attitudes towards patients, as well as patients' expectations regarding the appointment and his or her understanding after its completion. RESULTS: Patients showed higher enthusiasm after the appointment (4.47 +/- 0.06 versus 2.62 +/- 0.10) (mean +/- SEM), as well as some negative remarks such as in relation to the waiting time. The time spent in the consultation was 24.66 +/- 4.45 minutes (mean +/- SEM) and the waiting time was 123.09 +/- 4.91 minutes. The physician's written orientation was fairly well recalled by the patient when the doctor's letter could be previously understood. CONCLUSION: Patients benefit from physicians who keep the focus on them. In addition, this program stimulated the students for their accomplishment of the medical course.

Comparison of knowledge on asthma: doctors completing internal medicine residency and doctors completing medical school.

CONTEXT: Asthma has been reported as a disease of increasing prevalence. OBJECTIVE: To assess the level of information and knowledge about asthma by means of a questionnaire among recent graduate physicians applying for medical residency at the Clinical Hospital of the University of São Paulo Medical School, Brazil. DESIGN: 14 multiple-choice questions for asthma diagnosis and management. SETTING: University of São Paulo Medical School (FMUSP). PARTICIPANTS: Recent graduate physicians applying for the medical residency program at FMUSP in 1999 (n = 448) and physicians that had completed 2 year of internal medicine residency (n = 92). MAIN MEASUREMENTS: We applied a questionnaire with 14 multiple-choice questions about the management of asthma based upon the Expert Panel Report 2 - Guidelines for the Diagnosis and Management of Asthma, NIH/NHLBI, 1997 (EPR-2). RESULTS: The medical residency program in Internal Medicine improved treatment skills (the ability to propose adequate therapy) when compared to medical education (a score of 57.2% versus 46.9%, P < 0.001) but not diagnosis knowledge (understanding of asthma symptoms related to medicine intake) (33.5% versus 33.3%, P = 0.94). Treatment skills were higher among physicians who received their Medical Degree (MD) from public-sponsored medical schools in comparison with those from private schools [49.7 (SE 1.17)] versus [41.8 (SE 1.63)], P < 0.001. CONCLUSION: Medical schools might consider reevaluating their programs regarding asthma in order to improve medical assistance, especially when considering the general results for residents, as they were supposed to have achieved performance after completing this in-service training.

Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor.

Prolonged serum deprivation induces a structurally and functionally contractile phenotype in about 1/6 of cultured airway myocytes, which exhibit morphological elongation and accumulate abundant contractile apparatus-associated proteins. We tested the hypothesis that transcriptional activation of genes encoding these proteins accounts for their accumulation during this phenotypic transition by measuring the transcriptional activities of the murine SM22 and human smooth muscle myosin heavy chain promoters during transient transfection in subconfluent, serum fed or 7 day serum-deprived cultured canine tracheal smooth muscle cells. Contrary to our expectation, SM22 and smooth muscle myosin heavy chain promoter activities (but not viral murine sarcoma virus-long terminal repeat promoter activity) were decreased in long term serum-deprived myocytes by at least 8-fold. Because serum response factor (SRF) is a required transcriptional activator of these and other smooth muscle-specific promoters, we evaluated the expression and function of SRF in subconfluent and long term serum-deprived cells. Whole cell SRF mRNA and protein were maintained at high levels in serum-deprived myocytes, but SRF transcription-promoting activity, nuclear SRF binding to consensus CArG sequences, and nuclear SRF protein were reduced. Furthermore, immunocytochemistry revealed extranuclear redistribution of SRF in serum-deprived myocytes; nuclear localization of SRF was restored after serum refeeding. These results uncover a novel mechanism for physiological control of smooth muscle-specific gene expression through extranuclear redistribution of SRF and consequent down-regulation of its transcription-promoting activity.

Fas cross-linking induces apoptosis in human airway smooth muscle cells.

Hypertrophy and hyperplasia lead to excess accumulation of smooth muscle in the airways of human asthmatic subjects. However, little is known about mechanisms that might counterbalance these processes, thereby limiting the quantity of smooth muscle in airways. Ligation of Fas on the surface of vascular smooth muscle cells and nonmuscle airway cells can lead to apoptotic cell death. We therefore tested the hypotheses that 1) human airway smooth muscle (HASM) expresses Fas, 2) Fas cross-linking induces apoptosis in these cells, and 3) tumor necrosis factor (TNF)-alpha potentiates Fas-mediated airway myocyte killing. Immunohistochemistry using CH-11 anti-Fas monoclonal IgM antibody revealed Fas expression in normal human bronchial smooth muscle in vivo. Flow cytometry using DX2 anti-Fas monoclonal IgG antibody revealed that passage 4 cultured HASM cells express surface Fas. Surface Fas decreased partially during prolonged serum deprivation of cultured HASM cells and was upregulated by TNF-alpha stimulation. Fas cross-linking with CH-11 antibody induced apoptosis in cultured HASM cells, and this effect was reduced by long-term serum deprivation and synergistically potentiated by concomitant TNF-alpha exposure. TNF-alpha did not induce substantial apoptosis in the absence of Fas cross-linking. These data represent the first demonstration that Fas is expressed on HASM and suggest a mechanism by which Fas-mediated apoptosis could act to oppose excess smooth muscle accumulation during airway remodeling in asthma.

Divergent differentiation paths in airway smooth muscle culture: induction of functionally contractile myocytes.

We tested the hypothesis that prolonged serum deprivation would allow a subset of cultured airway myocytes to reacquire the abundant contractile protein content, marked shortening capacity, and elongated morphology characteristic of contractile cells within intact tissue. Passage 1 or 2 canine tracheal smooth muscle (SM) cells were grown to confluence, then serum deprived for up to 19 days. During serum deprivation, two differentiation pathways emerged. One-sixth of the cells developed an elongated morphology and aligned into bundles. Elongated myocytes contained cables of contractile myofilaments, dense bodies, gap junctions, and membrane caveoli, ultrastructural features of contractile SM in tissue. These cells immunostained intensely for SM alpha-actin, SM myosin heavy chain (MHC), and SM22 (an SM-specific actin-binding protein), and Western analysis of culture lysates disclosed 1.8 (SM alpha-actin)-, 7.7 (SM MHC)-, and 5.8 (SM22)-fold protein increases during serum deprivation. Immunoreactive M3 muscarinic receptors were present in dense foci distributed throughout elongated, SM MHC-positive myocytes. ACh (10(-3) M) induced a marked shortening (59.7 +/- 14.4% of original length) in 62% of elongated myocytes made semiadherent by gentle proteolytic digestion, and membrane bleb formation (a consequence of contraction) occurred in all stimulated cells that remained adherent and so did not shorten. Cultured airway myocytes that did not elongate during serum deprivation instead became short and flattened, lost immunoreactivity for contractile proteins, lacked the M3 muscarinic-receptor expression pattern seen in elongated cells, and exhibited no contractile response to ACh. Thus we demonstrate that prolonged serum deprivation induces distinct differentiation pathways in confluent cultured tracheal myocytes and that one subpopulation acquires an unequivocally functional contractile phenotype in which structure and function resemble contractile myocytes from intact tissue.

Transcriptional regulation of smooth muscle contractile apparatus expression.

The transcriptional regulatory mechanisms that control gene expression during differentiation and contractile protein accumulation are becoming well understood in skeletal and cardiac muscle lineages. Current understanding of smooth muscle-specific gene transcription is much more limited, though recent studies have begun to shed light on this topic. In this review, we summarize some of the themes emerging from these studies and identify transcriptional regulatory elements common to several smooth muscle genes. These include potential binding sites for serum response factor, Sp1, AP2, Mhox, and YY1, as well as a potential transforming growth factor-beta control element. We speculate that it may be possible to manipulate smooth muscle-specific gene expression in asthma or pulmonary arterial hypertension as an eventual therapy.

Expression and cytogenetic localization of the human SM22 gene (TAGLN).

SM22 is a 22-kDa protein identified variously as SM22, transgelin, WS3-10, or mouse p27. Though its precise function is unknown, it is abundant in smooth muscle and so may contribute to the physiology of this widespread tissue. We found that cosmid 16b6 contains the entire 5.4-kb, five-exon human SM22 gene (HGMW-approved symbol, TAGLN), and we cytogenetically localized the gene to chromosome 11q23.2. Northern analysis of human adult tissues showed that SM22 mRNA is most prevalent in smooth muscle-containing tissues, but is also found at lower levels in heart. The human SM22 promoter contains nuclear factor-binding motifs known to regulate transcription in smooth muscle, and human SM22 promoter-luciferase reporter constructs exhibited high transcriptional activity in A7r5 or primary canine aortic smooth muscle cells, but show little activity in nonmuscle COS7 cells. In addition, human SM22 promoter activity increased by two- to threefold upon serum stimulation of nonmuscle cells.

Airway responses to capsaicin in guinea pigs: role of NK-1 and NK-2 neurokinin receptors.

The role of NK-1 and NK-2 receptors on the pulmonary response to capsaicin in guinea pigs was evaluated using intravenous infusion of selective nonpeptide antagonists of NK 1 (CP 96345, 300 nmol/kg, and SR 140333, 300 nmol/kg) and NK-2 (SR 48968, 100 nmol/kg) neurokinin receptors. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (RL) after capsaicin infusion were significantly lower in the presence of SR 48968 (p < .005). Morphometric analysis of lungs obtained by quick-freezing showed significant attenuation of airway contraction and peribronchiolar edema formation in the presence of NK-2 antagonist (p < .001). When compared to guinea pigs that received only capsaicin, animals that received SR 140333 or CP 96345 showed lower values of Edyn, RL, airway contraction, and peribronchiolar edema, but only the difference in Edyn values was significant. The combination of NK-1 and NK-2 antagonists was not more effective than NK-2 antagonist alone in attenuating capsaicin effects. The results suggest that airway effects of capsaicin are mainly mediated by activation of NK-2 receptors although NK-1 receptors may also play a role.

Respiratory system, lung, and chest wall mechanics in guinea pigs.

1. Volume, airflow, tracheal, esophageal and transpulmonary pressures were measured in 6 mechanically ventilated, anesthetized and paralyzed guinea pigs. 2. The elastic and resistive properties of the respiratory system were partitioned into their lung and chest wall components a) following end-inflation occlusion of the airways subsequent to constant flow inspirations, and b) during relaxed expirations following release of occlusion. The values obtained by both methods were similar. 3. Mean respiratory system, lung and chest wall elastances were 3.518, 2.671, and 0.847 cm H2O/ml, respectively. 4. Mean respiratory system, pulmonary and chest wall resistances (at flows of 4.3 ml/s) were 0.302, 0.184, and 0.118 cm H2O ml-1 s, respectively. 5. Respiratory system, lung and chest wall resistances were partitioned into two components: 1) a homogeneous one whose values corresponded to 0.171, 0.095, and 0.076 cm H2O ml-1 s, for respiratory system, lung and chest wall, respectively, and 2) a component due to Pendelluft and stress relaxation and corresponding to 0.131, 0.089, and 0.042 cm H2O ml-1 s, respectively. 6. Resistive pressure vs flow relationships for the respiratory system, lung and chest wall were also determined during the entire tidal expiration. 7. We conclude that the chest wall participates significantly in respiratory system unevenness.

Influence of photoperiodism on cannabinoid content of Cannabis sativa L.

Cannabis sativa plants submitted to 10 and 12 hours of natural light showed different content in cannabinoids. An increase of exposure to natural light of only 2 hours a day, at least, doubled the average amoung of THC, but decreased that of cannabichromene.